1. Field of the Invention
This invention relates to acoustic assisted phase conjugate optical tomography.
2. Description of the Related Art
(Note: This application references a number of different publications as indicated throughout the specification by one or more reference numbers within brackets, e.g., [x]. A list of these different publications ordered according to these reference numbers can be found below in the section entitled “References.” Each of these publications is incorporated by reference herein.)
Deep-tissue clinical imaging techniques, such as ultrasound, magnetic resonance imaging (MRI) and X-ray imaging, provide clinicians with the means to visualize the interior structures of the scanned subject. While these methods are excellent at rendering contrast based on the structural characteristics of the tissues, their general limited ability to perform biochemical imaging poses a significant limitation to their realizable diagnostic potentials. As an example, consider the case of mammography screening for breast cancer. In such screenings, the clinician looks for suspicious lesion masses in the X-ray images. It is often difficult to judge if a mass is simply a benign calcified accumulation or a developing tumor [1]. To arrive at a conclusive diagnosis, a biopsy is required to surgically remove part of the tissues from the mass for further analysis. An imaging method that can provide additional biochemical information, such as HER2 (human epidermal growth factor receptor 2) presence or relative fat content [1], can dramatically improve the accuracy of such pre-biopsy analysis. More importantly, these biochemical changes can in principle be measured at an earlier progression stage that precedes formation of structural anomalies that are detectable by ultrasound, MRI and X-ray. The same consideration also applies for the screenings of cancer of the other organs, such as the prostate, liver, lungs and brain.
Similarly, the amount of real-time, in vivo information obtainable in vertebrate animal models by current methods is also limited. A high resolution, non-invasive, deep tissue imaging method would facilitate in vivo studies that may provide more insight to tissue and organ system development, disease progression and disease regression in the presence of therapeutics.
Optical methods offer excellent means for biochemical sensing. There is a wealth of light-matter interaction mechanisms, such as fluorescence [2], absorption [3], Raman scattering [1], as well as nonlinear light interactions [4], which can be used to perform biochemical specific sensing and measurements.
Despite the biochemical sensing advantage, the conventional optical methods are unable to accomplish optical imaging with a resolution better than 100 microns in tissues that are thicker than a couple of millimeters. Optical-based deep tissue imaging is largely impeded by the fact that biological tissues scatter light very strongly. As a point of reference, the mean scattering length of 633 nm light in dermis is 50 microns, while the mean absorption length is 3.7 mm [5]. Much like the case of fog, tissue turbidity obscures the line of sight by diffusing light and preventing the forming of an optical focus.
In recent years, several biophotonics imaging approaches have been developed to push the optical imaging depth limit. Here is a summary of some of the more promising approaches:
1. Optical Coherence Tomography (OCT) [6]. OCT has excellent resolution (˜ microns) but relatively limited imaging depth (typically 1 mm). Additionally, OCT renders mostly structural information-based or flow-based images and is not well suited to collect fluorescence or Raman information.
2. Diffuse optical tomography (DOT) [7]. This approach comprises a wide range of techniques and innovations. Broadly speaking, DOT sends light through the target tissue and carefully measures the resulting transmission from a number of exit points. DOT then renders a relatively low resolution ‘best-guess’ image of the tissue. DOT can work with thick tissues, but its resolution is fairly low (>1 mm). The biochemical-associated information collected is largely absorption spectrum based.
3. Ultrasound-modulated optical tomography (UOT) [8]. In this method, an ultrasound beam is brought to a focus within the target tissue which is illuminated by light. The transmitted light field will carry a modulated component, which correlates to the light field component that has passed through that ultrasound focal point. By scanning the ultrasound focus through the tissue and measuring the modulation strength in the transmitted light field, an image of the sample can then be rendered. The imaging depth for such a strategy is high (˜ cm) and the resolution corresponds to the ultrasound focal spot size (˜10's to 100 microns). Unfortunately, the much sought modulation is associated with a high background signal that significantly degrades sensitivity.
4. Photoacoustic tomography (PAT) [3]. In PAT, the target tissue is illuminated with a pulsed laser source. The laser pulse is absorbed by absorbers in the tissue and induces rapid thermal-expansion at the absorber site. The generated acoustic waves are then detected and measured by an array of ultrasound transducer at the tissue's boundaries. This method has a large imaging depth (˜1 cm) and the resolution achieved can also be high (˜100 microns). The biochemical information gathered is largely absorption-based.